{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:18:50Z","timestamp":1792091930036,"version":"4.4.0"},"reference-count":21,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T00:00:00Z","timestamp":1532044800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01AI12140"],"award-info":[{"award-number":["R01AI12140"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008296","name":"Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University","doi-asserted-by":"publisher","award":["Grant# 477482)"],"award-info":[{"award-number":["Grant# 477482)"]}],"id":[{"id":"10.13039\/100008296","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Materials"],"abstract":"<jats:p>Vancomycin is the treatment of choice for infections caused by methicillin-resistant Staphylococcus aureus (MRSA). Clinically, combinations of vancomycin (VAN) and beta-lactams have been shown to improve patient outcomes compared to VAN alone for the treatment of MRSA bloodstream infections. However, VAN is known to cause nephrotoxicity, which could be ameliorated using biocompatible lipid drug delivery systems or liposomes. Previous attempts have been made for encapsulation of VAN in liposomes; however, drug loading has been poor, mainly because of the high aqueous solubility of VAN. In this study, we report a robust method to achieve high loading of VAN and cefazolin (CFZ) in unilamellar liposomes. Liposomes of sizes between 170\u2013198 nm were prepared by modified reverse phase evaporation method and achieved high loading of 40% and 26% (weight\/weight) for VAN and CFZ, respectively. Liposomal VAN reduced minimum inhibitory concentration (MIC) values 2-fold in comparison to commercial VAN. The combination of liposomal VAN (LVAN) and liposomal CFZ (LCFZ) demonstrated a 7.9-fold reduction compared to LVAN alone. Rhodamine dye-loaded liposomes demonstrated superior cellular uptake in macrophage-like RAW 264.7 cells. Fluorescent images of LVAN-encapsulating near-infrared (NIR) dye, S0456 (LVAN-S0456) clearly indicated that LVAN-S0456 had reduced renal excretion with very low fluorescent intensity in the kidneys. It is anticipated that the long circulation and reduced kidney clearance of LVAN-S0456 compared to VAN-S0456 injected in mice can lead to enhanced efficacy against MRSA infections with reduced nephrotoxicity. Overall, our developed formulations of VAN when administered alone or in combination with CFZ, provide a rational approach for combating MRSA infections.<\/jats:p>","DOI":"10.3390\/ma11071245","type":"journal-article","created":{"date-parts":[[2018,7,20]],"date-time":"2018-07-20T02:10:11Z","timestamp":1532052611000},"page":"1245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Combination of Vancomycin and Cefazolin Lipid Nanoparticles for Overcoming Antibiotic Resistance of MRSA"],"prefix":"10.3390","volume":"11","author":[{"given":"Ketki","family":"Bhise","sequence":"first","affiliation":[{"name":"Use-Inspired Biomaterials &amp; Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4364-5875","authenticated-orcid":false,"given":"Samaresh","family":"Sau","sequence":"additional","affiliation":[{"name":"Use-Inspired Biomaterials &amp; Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Razieh","family":"Kebriaei","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seth A.","family":"Rice","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyle C.","family":"Stamper","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5448-1004","authenticated-orcid":false,"given":"Hashem O.","family":"Alsaab","sequence":"additional","affiliation":[{"name":"Use-Inspired Biomaterials &amp; Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael J.","family":"Rybak","sequence":"additional","affiliation":[{"name":"Anti-Infective Research Laboratory, Department of Pharmacy Practice, Eugene Applebaum College of Pharmacy and Health Sciences, Wayne State University, Detroit, MI 48201, USA"},{"name":"Department of Pharmacy Services, Detroit Medical Center, Detroit, MI 48201, USA"},{"name":"Department of Medicine, Division of Infectious Diseases, School of Medicine, Wayne State University, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4428-0222","authenticated-orcid":false,"given":"Arun K.","family":"Iyer","sequence":"additional","affiliation":[{"name":"Use-Inspired Biomaterials &amp; Integrated Nano Delivery (U-BiND) Systems Laboratory, Department of Pharmaceutical Sciences, Wayne State University, Detroit, MI 48201, USA"},{"name":"Molecular Imaging Program, Karmanos Cancer Institute, Detroit, MI 48201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,7,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/S1473-3099(05)70086-4","article-title":"Lack of development of new antimicrobial drugs: A potential serious threat to public health","volume":"5","author":"Norrby","year":"2005","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"e00157-18","DOI":"10.1128\/AAC.00157-18","article-title":"\u03b2-Lactam Combinations with Vancomycin Show Synergistic Activity against Vancomycin-Susceptible Staphylococcus aureus, Vancomycin-Intermediate S. aureus (VISA), and Heterogeneous VISA","volume":"62","author":"Tran","year":"2018","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1128\/AAC.05473-11","article-title":"In vitro pharmacodynamics of vancomycin and cefazolin alone and in combination against methicillin-resistant Staphylococcus aureus","volume":"56","author":"Hagihara","year":"2012","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"363","DOI":"10.1016\/j.diagmicrobio.2018.03.020","article-title":"Impact of cefazolin co-administration with vancomycin to reduce development of vancomycin-intermediate Staphylococcus aureus","volume":"91","author":"Singh","year":"2018","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"653","DOI":"10.1002\/phar.1423","article-title":"Vancomycin-associated nephrotoxicity in adult medicine patients: Incidence, outcomes, and risk factors","volume":"34","author":"Meaney","year":"2014","journal-title":"Pharmacotherapy"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"812","DOI":"10.1016\/j.drudis.2006.07.005","article-title":"Exploiting the enhanced permeability and retention effect for tumor targeting","volume":"11","author":"Iyer","year":"2006","journal-title":"Drug Discov. Today"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"506","DOI":"10.1016\/j.ijpharm.2017.04.078","article-title":"Nanostructured lipid carriers employing polyphenols as promising anticancer agents: Quality by design (QbD) approach","volume":"526","author":"Bhise","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"104928","DOI":"10.18632\/oncotarget.20650","article-title":"A CARP-1 functional mimetic loaded vitamin E-TPGS micellar nano-formulation for inhibition of renal cell carcinoma","volume":"8","author":"Cheriyan","year":"2017","journal-title":"Oncotarget"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1016\/j.colsurfb.2017.06.025","article-title":"Folic acid conjugated polymeric micelles loaded with a curcumin difluorinated analog for targeting cervical and ovarian cancers","volume":"157","author":"Luong","year":"2017","journal-title":"Colloids Surf. B Biointerface"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1016\/j.drudis.2017.05.011","article-title":"Advances in antibody-drug conjugates: A new era of targeted cancer therapy","volume":"22","author":"Sau","year":"2017","journal-title":"Drug Discov. Today"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Tatiparti, K., Sau, S., Kashaw, S., and Iyer, A. (2017). siRNA Delivery Strategies: A Comprehensive Review of Recent Developments. Nanomaterials, 7.","DOI":"10.3390\/nano7040077"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1197","DOI":"10.1021\/acs.biomac.6b01885","article-title":"Polyvalent Folate-Dendrimer-Coated Iron Oxide Theranostic Nanoparticles for Simultaneous Magnetic Resonance Imaging and Precise Cancer Cell Targeting","volume":"18","author":"Luong","year":"2017","journal-title":"Biomacromolecules"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1003","DOI":"10.4155\/tde-2017-0062","article-title":"Nanomedicine for cancer diagnosis and therapy: Advancement, success and structure-activity relationship","volume":"8","author":"Bhise","year":"2017","journal-title":"Ther. Deliv."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"251","DOI":"10.1080\/026520499289220","article-title":"Preparation of liposomes by reverse-phase evaporation using alternative organic solvents","volume":"16","author":"Cortesi","year":"1999","journal-title":"J. Microencapsul."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1441","DOI":"10.1016\/j.nano.2018.04.004","article-title":"CD44 Directed Nanomicellar Payload Delivery Platform for Selective Anticancer Effect and Tumor Specific Imaging of Triple Negative Breast Cancer","volume":"14","author":"Ms","year":"2018","journal-title":"Nanomedicine"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Kubica, M., Guzik, K., Koziel, J., Zarebski, M., Richter, W., Gajkowska, B., Golda, A., Maciag-Gudowska, A., Brix, K., and Shaw, L. (2008). A potential new pathway for Staphylococcus aureus dissemination: The silent survival of S. aureus phagocytosed by human monocyte-derived macrophages. PLoS ONE, 3.","DOI":"10.1371\/journal.pone.0001409"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1038\/s41551-017-0187-5","article-title":"Antibiotic-loaded nanoparticles targeted to the site of infection enhance antibacterial efficacy","volume":"2","author":"Hussain","year":"2018","journal-title":"Nat. Biomed. Eng."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"101","DOI":"10.4103\/0255-0857.148402","article-title":"Anti-biofilm efficacy of silver nanoparticles against MRSA and MRSE isolated from wounds in a tertiary care hospital","volume":"33","author":"Ansari","year":"2015","journal-title":"Indian J. Med. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"176","DOI":"10.1016\/j.ijpharm.2017.03.033","article-title":"Vancomycin-loaded nanobubbles: A new platform for controlled antibiotic delivery against methicillin-resistant Staphylococcus aureus infections","volume":"523","author":"Argenziano","year":"2017","journal-title":"Int. J. Pharm."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fphar.2017.00561","article-title":"PD-1 and PD-L1 checkpoint signaling inhibition for cancer immunotherapy: Mechanism, combinations, and clinical outcome","volume":"8","author":"Alsaab","year":"2017","journal-title":"Front. Pharmacol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1016\/j.jconrel.2018.01.028","article-title":"Multifunctional nanoparticles for cancer immunotherapy: A groundbreaking approach for reprogramming malfunctioned tumor environment","volume":"274","author":"Sau","year":"2018","journal-title":"J. Control. Release"}],"container-title":["Materials"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1996-1944\/11\/7\/1245\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T15:13:13Z","timestamp":1760195593000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1996-1944\/11\/7\/1245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,7,20]]},"references-count":21,"journal-issue":{"issue":"7","published-online":{"date-parts":[[2018,7]]}},"alternative-id":["ma11071245"],"URL":"https:\/\/doi.org\/10.3390\/ma11071245","relation":{},"ISSN":["1996-1944"],"issn-type":[{"value":"1996-1944","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,7,20]]}}}